This invention relates generally to the measurement of blood flow and, more particularly, to the measurement of blood flow using non-radioactively labeled microspheres.
The measurement of blood flow in experimental animals is often necessary in the fields of pharmacology, physiology, therapeutics and diagnostics. For example, toxicology studies require blood flow measurement to determine the toxicity of various suspected toxic agents. Further, virtually all diagnostic and therapeutic advances impact on blood flow in some manner. It is therefore desirable to take blood flow measurements.
Blood flow measurements can be performed in many anatomical areas, including the brain, heart, lung, gut, kidney, reproductive organs, skin and muscle. The most sensitive and specific technique used today for measuring blood flow involves the use of radioactively labeled microspheres. In one particular technique, plastic microspheres are marked with a radioactive label and injected into the left atrium of an experimental animal. The spheres disperse in proportion to blood flow. The animal is then sacrificed and the organ of interest is harvested. Blood flow to a particular organ is determined by measuring the level of radioactivity in the organ, which is a function of the number of spheres trapped in the organ's capillaries.
Although the use of radioactively labeled microspheres is sensitive and specific, there are several problems and disadvantages associated with this method. First, startup costs are very high, as they include purchase of a gamma counter to measure radioactivity, lead shielding to protect lab workers from radiation exposure, complex storage facilities and a high minimum "per order" cost of equipment from manufacturers. These high costs severely limit the availability of this type of blood flow measuring apparatus to large labs only.
Second, only five to eight successive measurements per animal can be made using radioactively labeled microspheres, due to the overlap between energies of available radiolabels. Moreover, the measurement of even five blood flow stages requires the use of an extremely complex computer program to analyze and separate the data obtained, further limiting the availability of the technique.
Third, radiolabeled spheres have a limited shelf-life, ranging from one week to several months. Even where the shelf life is at the high end of this range, the continuous decay makes continual recalibration of the testing apparatus necessary.
Fourth, laboratory workers using this apparatus are exposed to substantial radiation danger because many of the isotopes used as labels emit high levels of energy and have long half-lives. In addition, the costs involved in minimizing radiation exposure are substantial.
Finally, disposal of the experimental animals poses significant problems, both logistically and financially. Since the animals remain radioactive for several years after disposal, they must be placed in special low level radiation dumps, to which there is increasing public resistance. The cost of disposal is also becoming prohibitive, recently reaching as high as $500 per animal.
What is needed, therefore, is a method of measuring blood flow that is sensitive and specific, yet is inexpensive to use and does not have the problems associated with a radioactively based method. The present invention satisfies these needs and provides other related advantages.